Minor Ailment Pharmacology Flashcards
What is the MOA of decongestants and what are some examples?
Decongestants are A-1 adrenergic receptor agonists that act in the nasal mucosa to produce vasoconstriction
Vasoconstriction decreases resistance to airflow and improves ventilation by decreasing the volume of nasal mucosa and reduced delivery and secretion of fluids to the nasal mucosa
Examples: ephedrine, pseudophedrine, and phenylephrine
What are the differences between ephedrine, pseudoephedrine, and phenylephrine?
Ephedrine → directly stimulates A-1 and B adrenergic receptors so it causes bronchial relaxation, increased HR and contractility, and enhances release of NE from sympathetic neurons
Pseudoephedrine → directly stimulates A-1 and B receptors but is less potent in producing tachycardia, increasing BP and CNS activation
Phenylephrine → selective A-1 agonist
What is the difference in the onset of action for oral vs topical decongestants?
Oral = 30 min
Topical = 5-10 min
Topical products also come in long acting (dosed 2x day) and short acting (dosed every 4h) versions
What is the MOA of an antitussive and what are some examples?
Acts on the medulla to increase cough threshold and suppress cough
Codeine → acts on opioid receptors in the medullary cough center, little effectiveness at OTC doses and AEs include sedation and constipation
Dextromethorphan → chemically similar to codeine with no analgesic or euphoric properties, does not act on opioid receptors but acts centrally to elevate threshold for coughing, fewer side effects than codeine
What is the MOA for expectorants and what is an example?
MOA: thought to stimulate respiratory tract secretions, thereby increasing respiratory fluid volumes and decreasing mucous viscosity; should help get phlegm out by coughing
Guaifenesin → little evidence for efficacy and no evidence for adverse effects or drug interactions
Where is histamine primarily stored?
Mast cells
Mast cells are found in large numbers in the skin, bronchial mucosa, intestinal mucosa, and basophils
Explain the mechanism histamine being released from storage granules in an allergic response
- Antigen interacts with IgE antibodies on the surface of mast cells
- Leads to the production of IP3 which increases cellular calcium
- Calcium causes exocytosis of the content of secretory granules
- This leads to the release of histamine, as well as release and production of other allergic mediators like leukotrienes
Where are H1 receptors found and what do they do?
H1 receptors are distributed widely in CNS and periphery, particularly on smooth muscle and endothelial cells
Many of the common effects of histamine are due to activation of the H1 receptors (itching, stimulation of nasal secretion, sedation associated with antihistamines)
Where are H2 receptors found?
Distributed in gastric parietal cells, cardiac muscle, mast cells and in the CNS
What are H3 receptors?
Auto-receptors on histamine-containing neurons
activation inhibits further histamine release
What are the vascular and other effects of Histamine?
- dilation of resistance vessels - involves H1 and H2
- constriction of veins due to activation of H1 receptors on vascular smooth muscle, contributes to extravastion of fluid and edema
- Increased capillary permeability which also contributes to edema
- Large amounts of histamine (like in anaphylaxis) cause profound reduction in blood pressure due to vasodilation and plasma escape from circulation
Other:
- altered cardiac contractility and electrical conductance (via H1 and H2)
- contraction of non-vascular smooth muscle (H1) contributes to bronchoconstriction in patients with asthma
- wheal formation, itching, pain
What are the two main differences between 1st and 2nd generation of antihistamines?
- 1st gen can cross the blood brain barrier and 2nd gen cannot
- 1st gen are not selective for H1 receptors and also block muscarinic receptors giving anticholinergic side effects
What is an eicosandoid?
Lipid signalling molecule related to or derived from arachidonic acid
Net effect on a particular tissue involves both the number and type of eicosanoid receptor and the type and concentration of eicosanoid present
What is a prostanoid?
Primarily derived via the actions of COX (enzyme that converts arachidonic acid into PGH2)
Other prostanoids are metabolites of PGH2
What is a leukotriene?
Derived from HPETE which is produced from arachidonic acid by lipoxygenase, additional synthase, hydrolase, and dipeptidase enzymes then convert HPETE into additional leukotrienes
How does inflammation and swelling happen? What is the purpose?
Inflammation → release of local inflammatory mediators and accumulation of neutrophils as the primary WBC
Swelling → movement of plasma into the area of inflammation
This dilutes toxins, initiates blood clotting to prevent anything from reaching the rest of the body
What does a local inflammatory hormone do and what are some examples?
Some can directly stimulate sensory pain neurons (histamine, bradykinins)
Some reduce threshold for firing (histamine, prostaglandins)
What is the MOA of acetaminophen?
Centrally produces a fever-reducing activity via inhibition of COX in the thermoregulatory center
Inhibits synthesis and release of prostaglandins in the thermoregulatory center of the anterior hypothalamus to reverse fever-inducing actions
What is the MOA for NSAIDs?
NSAIDs inhibit COX to prevent conversion of arachidonic acid to PGH2 thus preventing subsequent prostaglandin production; anti-inflammatory effects but not related to cortisol
What are the differences between ibuprofen and naproxen?
Ibuprofen is better tolerated than aspirin, has a half life of 2-4 hours, and is equally potent for COX1 and COX2 receptors
Naproxen has a longer half-life at ~14 hours and is slightly COX1 selective
How do corticosteroids have anti-inflammatory actions and what else are they used for?
Corticosteroids inhibit phospholipase A2, the first enzyme in the arachidonic acid cascade
Inhibition of arachidonic acid also inhibits the production of its metabolites including prostaglandins, bradykinins and leukotrienes
Also used for disease states involving the immune system (autoimmune disorders and any inflammatory condition including acute and chronic pain)
How do H2 histamine receptor antagonists reduce stomach acid?
Competitively and very selectively block the H2 receptors on parietal cells
Inhibits all acid secretion but the highest efficacy is nocturnal
What does a bismuth compound do?
- coats and erosions and ulcers
- stimulates prostaglandin production
- stimulates mucous and bicarbonate secretion
- decreases GI secretions to treat diarrhea
- direct antimicrobial effects
How does loperamide work to treat diarrhea?
It is an opioid receptor agonist that reduces tone of GI smooth muscle to cause constipation
Limited CNS effects
